The NDNF-like factor Nord is a Hedgehog-induced extracellular BMP modulator that regulates Drosophila wing patterning and growth
- George Washington University, United States
- University of Minnesota, United States
Abstract
Hedgehog (Hh) and bone morphogenetic proteins (BMPs) pattern the developing Drosophila wing by functioning as short- and long-range morphogens, respectively. Here, we show that a previously unknown Hh-dependent mechanism fine-tunes the activity of BMPs. Through genome-wide expression profiling of the Drosophila wing imaginal discs, we identify nord as a novel target gene of the Hh signaling pathway. Nord is related to the vertebrate Neuron Derived Neurotrophic Factor (NDNF) involved in Congenital Hypogonadotropic Hypogonadism and several types of cancer. Loss- and gain-of-function analyses implicate Nord in the regulation of wing growth and proper crossvein patterning. At the molecular level, we present biochemical evidence that Nord is a secreted BMP-binding protein and localizes to the extracellular matrix. Nord binds to Decapentaplegic (Dpp) or the heterodimer Dpp-Glass bottom boat (Gbb) to modulate their release and activity. Furthermore, we demonstrate that Nord is a dosage-depend BMP modulator, where low levels of Nord promote and high levels inhibit BMP signaling. Taken together, we propose that Hh-induced Nord expression fine tunes both the range and strength of BMP signaling in the developing Drosophila wing.
Data availability
The raw microarray data were deposited to the Gene Expression Omnibus public repository (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE180120; Gene Expression Omnibus series no. GSE180120).
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Genome-wide expression profiling in Drosophila wing imaginal discsNCBI Gene Expression Omnibus, GSE180120.
Article and author information
Author details
Michael B O'Connor
Funding
NIGMS (R01GM117440)
- Xiaoyan Zheng
NIGMS (R35GM118029)
- Michael B O'Connor
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Erika A Bach, New York University School of Medicine, United States
Version history
- Received: August 25, 2021
- Preprint posted: September 6, 2021 (view preprint)
- Accepted: January 15, 2022
- Accepted Manuscript published: January 17, 2022 (version 1)
- Version of Record published: February 18, 2022 (version 2)
Copyright
© 2022, Yang et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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The NDNF-like factor Nord is a Hedgehog-induced extracellular BMP modulator that regulates Drosophila wing patterning and growth
eLife 11:e73357.
https://doi.org/10.7554/eLife.73357
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